Frontiers in Cellular Neuroscience (Feb 2018)
A Fat-Facets-Dscam1-JNK Pathway Enhances Axonal Growth in Development and after Injury
- Marta Koch,
- Marta Koch,
- Maya Nicolas,
- Maya Nicolas,
- Marlen Zschaetzsch,
- Marlen Zschaetzsch,
- Natalie de Geest,
- Natalie de Geest,
- Annelies Claeys,
- Annelies Claeys,
- Jiekun Yan,
- Jiekun Yan,
- Matthew J. Morgan,
- Matthew J. Morgan,
- Maria-Luise Erfurth,
- Maria-Luise Erfurth,
- Matthew Holt,
- Matthew Holt,
- Dietmar Schmucker,
- Dietmar Schmucker,
- Bassem A. Hassan,
- Bassem A. Hassan,
- Bassem A. Hassan
Affiliations
- Marta Koch
- Laboratory of Neurogenetics, Center for Brain and Disease Research, Vlaams Instituut voor Biotechnologie (VIB), Leuven, Belgium
- Marta Koch
- Center for Human Genetics, University of Leuven School of Medicine, KU Leuven, Leuven, Belgium
- Maya Nicolas
- Laboratory of Neurogenetics, Center for Brain and Disease Research, Vlaams Instituut voor Biotechnologie (VIB), Leuven, Belgium
- Maya Nicolas
- Center for Human Genetics, University of Leuven School of Medicine, KU Leuven, Leuven, Belgium
- Marlen Zschaetzsch
- Laboratory of Neurogenetics, Center for Brain and Disease Research, Vlaams Instituut voor Biotechnologie (VIB), Leuven, Belgium
- Marlen Zschaetzsch
- Center for Human Genetics, University of Leuven School of Medicine, KU Leuven, Leuven, Belgium
- Natalie de Geest
- Laboratory of Neurogenetics, Center for Brain and Disease Research, Vlaams Instituut voor Biotechnologie (VIB), Leuven, Belgium
- Natalie de Geest
- Center for Human Genetics, University of Leuven School of Medicine, KU Leuven, Leuven, Belgium
- Annelies Claeys
- Laboratory of Neurogenetics, Center for Brain and Disease Research, Vlaams Instituut voor Biotechnologie (VIB), Leuven, Belgium
- Annelies Claeys
- Center for Human Genetics, University of Leuven School of Medicine, KU Leuven, Leuven, Belgium
- Jiekun Yan
- Laboratory of Neurogenetics, Center for Brain and Disease Research, Vlaams Instituut voor Biotechnologie (VIB), Leuven, Belgium
- Jiekun Yan
- Center for Human Genetics, University of Leuven School of Medicine, KU Leuven, Leuven, Belgium
- Matthew J. Morgan
- Laboratory of Neurogenetics, Center for Brain and Disease Research, Vlaams Instituut voor Biotechnologie (VIB), Leuven, Belgium
- Matthew J. Morgan
- Center for Human Genetics, University of Leuven School of Medicine, KU Leuven, Leuven, Belgium
- Maria-Luise Erfurth
- Center for Human Genetics, University of Leuven School of Medicine, KU Leuven, Leuven, Belgium
- Maria-Luise Erfurth
- Neuronal Wiring Lab, Center for Brain and Disease Research, Vlaams Instituut voor Biotechnologie (VIB), Leuven, Belgium
- Matthew Holt
- Center for Human Genetics, University of Leuven School of Medicine, KU Leuven, Leuven, Belgium
- Matthew Holt
- Laboratory of Glia Biology, Center for Brain and Disease Research, Vlaams Instituut voor Biotechnologie (VIB), Leuven, Belgium
- Dietmar Schmucker
- Center for Human Genetics, University of Leuven School of Medicine, KU Leuven, Leuven, Belgium
- Dietmar Schmucker
- Neuronal Wiring Lab, Center for Brain and Disease Research, Vlaams Instituut voor Biotechnologie (VIB), Leuven, Belgium
- Bassem A. Hassan
- Laboratory of Neurogenetics, Center for Brain and Disease Research, Vlaams Instituut voor Biotechnologie (VIB), Leuven, Belgium
- Bassem A. Hassan
- Center for Human Genetics, University of Leuven School of Medicine, KU Leuven, Leuven, Belgium
- Bassem A. Hassan
- Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut du Cerveau et de la Moelle Epinière, Hôpital Pitié-Salpêtrière, UPMC, Sorbonne Universités, Paris, France
- DOI
- https://doi.org/10.3389/fncel.2017.00416
- Journal volume & issue
-
Vol. 11
Abstract
Injury to the adult central nervous systems (CNS) can result in severe long-term disability because damaged CNS connections fail to regenerate after trauma. Identification of regulators that enhance the intrinsic growth capacity of severed axons is a first step to restore function. Here, we conducted a gain-of-function genetic screen in Drosophila to identify strong inducers of axonal growth after injury. We focus on a novel axis the Down Syndrome Cell Adhesion Molecule (Dscam1), the de-ubiquitinating enzyme Fat Facets (Faf)/Usp9x and the Jun N-Terminal Kinase (JNK) pathway transcription factor Kayak (Kay)/Fos. Genetic and biochemical analyses link these genes in a common signaling pathway whereby Faf stabilizes Dscam1 protein levels, by acting on the 3′-UTR of its mRNA, and Dscam1 acts upstream of the growth-promoting JNK signal. The mammalian homolog of Faf, Usp9x/FAM, shares both the regenerative and Dscam1 stabilizing activities, suggesting a conserved mechanism.
Keywords
- axonal growth
- axonal injury
- post-transcriptional reguylatiopn
- Central nervous system
- Drosophila melanogaster
